Zhao Fei, Obermann Sonja, von Wasielewski Reinhard, Haile Lydia, Manns Michael P, Korangy Firouzeh, Greten Tim F
Department of Gastroenterology, Hepatology and Endocrinology, Medical School Hannover, Hannover, Germany.
Immunology. 2009 Sep;128(1):141-9. doi: 10.1111/j.1365-2567.2009.03105.x.
Pancreatic adenocarcinoma is one of the deadliest cancers with poor survival and limited treatment options. Immunotherapy is an attractive option for this cancer that needs to be further developed. Tumours have evolved a variety of mechanisms to suppress host immune responses. Understanding these responses is central in developing immunotherapy protocols. The aim of this study was to investigate potential immune suppressor mechanisms that might occur during development of pancreatic tumours. Myeloid-derived suppressor cells (MDSC) from mice with spontaneous pancreatic tumours, mice with premalignant lesions as well as wild-type mice were analysed. An increase in the frequency of MDSC early in tumour development was detected in lymph nodes, blood and pancreas of mice with premalignant lesions and increased further upon tumour progression. The MDSC from mice with pancreatic tumours have arginase activity and suppress T-cell responses, which represent the hallmark functions of these cells. Our study suggests that immune suppressor mechanisms generated by tumours exist as early as premalignant lesions and increase with tumour progression. These results highlight the importance of blocking these suppressor mechanisms early in the disease in developing immunotherapy protocols.
胰腺腺癌是最致命的癌症之一，生存率低且治疗选择有限。免疫疗法是这种癌症颇具吸引力的一种选择，有待进一步开发。肿瘤已经进化出多种机制来抑制宿主免疫反应。了解这些反应是制定免疫治疗方案的核心。本研究的目的是调查胰腺肿瘤发生过程中可能出现的潜在免疫抑制机制。对来自患有自发性胰腺肿瘤的小鼠、患有癌前病变的小鼠以及野生型小鼠的髓源性抑制细胞（MDSC）进行了分析。在患有癌前病变的小鼠的淋巴结、血液和胰腺中，在肿瘤发生早期就检测到MDSC频率增加，并且在肿瘤进展时进一步增加。来自患有胰腺肿瘤的小鼠的MDSC具有精氨酸酶活性并抑制T细胞反应，这代表了这些细胞的标志性功能。我们的研究表明，肿瘤产生的免疫抑制机制早在癌前病变阶段就已存在，并随着肿瘤进展而增加。这些结果凸显了在疾病早期阻断这些抑制机制对于制定免疫治疗方案的重要性。
